Aqp1 of 270 aas and 6 TMSs. Induced by NH3 but not CO2, but transports both gases. Aqp1 is found in the plasma membrae as well as the ER/chloroplast. Aqp1 may be involved in photoprotection. It may facilitate the efflux of NH3, preventing the uncoupling effect of high intracellular ammonia concentrations (Matsui et al. 2018).

FPS1 glycerol efflux facilitator (important for maintaining osmotic balance during mating-induced yeast cell fusion and for tolerating hypoosmotic shock; also transports arsenite and antimonite). FPS1 is a homotetramer (Beese-Sims et al., 2011). Fps1 is important for osmo-adaptation by regulating intracellular glycerol levels during changes in external osmolarity. Upon high osmolarity conditions, yeast accumulate glycerol by increased production of the osmolyte and by restricting glycerol efflux through Fps1. The extended cytosolic termini of Fps1 contain short domains that are important for regulating glycerol flux through the channel. The transmembrane core of the protein plays an equally important role (Geijer et al., 2012). The MAP kinase, Slt2, physically interacts
with Fps1, and this interaction, dependent on phosphorylation of S537, regulates arsenite uptake (Ahmadpour et al. 2016).

Aquaporin, Aqy1 (PIP2-7 7). The subangstron (0.88Å) structure is available (Kosinska Eriksson et al. 2013). the H-bond donor interactions of the NPA motif''s asparagine residues to
passing water molecules are revealed. A polarized water-water H-bond
configuration is observed within the channel. Four selectivity filter water positions
are too closely spaced to be simultaneously occupied. Strongly correlated
movements break the connectivity of selectivity filter water molecules to other water molecules
within the channel, thereby preventing proton transport via a Grotthuss
mechanism.

Aquaporin-4 (AQP4) is the major water channel in the central nervous system and plays an important role in the brain's water balance, including edema formation and clearance. There are 6 splice variants; the shorter ones assemble into functional, tetrameric square arrays; the longer is palmitoylated on N-terminal cysteyl residues) (Suzuki et al., 2008). The longest, Aqp4e, has a novel N-terminal domain and forms a water channel in the plasma membrane although various shorter variants don't (Moe et al., 2008). AQP4, like AQP0 (1.A.8.8.2), forms water channels but also forms adhesive junctions (Engel et al., 2008) (causes cytotoxic brain swelling in mice (Yang et al., 2008)) Mice lacking Aqp4 have impaired olfactions (Lu et al., 2008). Aqp4 is down regulated in skeletal muscle in muscular dystrophy (Au et al. 2008). The crystal structure is known to 2.8 Å resolution (Tani et al., 2009). The structure reveals 8 water molecules in each of the four channels, supporting a hydrogen-bond isolation mechanism and explains its fast and selective water conduction and proton exclusion (Tani et al., 2009; Cui and Bastien, 2011). It is an important antigen in Neuromyelitis optica (NMO) patients (Kalluri et al., 2011). A connection has been made between AQP4-mediated fluid accumulation and post traumatic syringomyelia (Hemley et al. 2013). AQP4 has increased water
permeability at low pH, and His95 is the pH-dependent gate (Kaptan et al. 2015). Also transports NH3 but not NH4+ (Assentoft et al. 2016). Cerebellar damage following status epilepticus involves down regulation of AQP4 expression (Tang et al. 2017). SUR1-TRPM4 and AQP4 form a complex to increase bulk water influx during astrocyte swelling (Stokum et al. 2017). A mutation, S111T, causes intellectual disability, hearing loss, and progressive gait dysfunction (Berland et al. 2018). As in humans, the chicken ortholog, Aqp4, is found in brain > kidney > stomach (Ramírez-Lorca et al. 2006). A Molecular Dynamics Investigation on Human AQP4 has been published (Marracino et al. 2018).

Vasopressin-sensitive aquaporin-2 (Aqp2) in the apical membrane of the renal collecting duct (Fenton et al., 2008). Controls cell volume and thereby influences cell proliferation (Di Giusto et al. 2012). It plays a
key role in concentrating urine. Water reabsorption is regulated by AQP2 trafficking between
intracellular storage vesicles and the apical membrane. This process is tightly controlled by the
pituitary hormone arginine vasopressin, and defective trafficking results in nephrogenic diabetes
insipidus (NDI). The crystal structure of Aqp2 has been solved to 2.75Å (Frick et al. 2014). In terrestrial vertebrates, AQP2 function is generally regulated by arginine-vasopressin to
accomplish key functions in osmoregulation such as the maintenance of body water
homeostasis by a cyclic AMP-independent mechanism (Olesen and Fenton 2017; Martos-Sitcha et al. 2015). AQP2 is expressed in the anterior vaginal wall and fibroblasts, and regulates the expression level of collagen I/III i, suggesting that AQP2 is associated with the pathogenesis of stress urinary incontinence through collagen metabolism during ECM remodeling (Zhang et al. 2017). As in humans, the chicken ortholog, Aqp2, is found only in the kidney (Ramírez-Lorca et al. 2006).

Water channel, Aqp1; inhibited by HgCl2 and tetraethylammonium. Plays a role in water homeostasis during blood feeding and humidity adaptation of A. gambiae, a major mosquito vector of human malaria in Africa (Liu et al., 2011).

Aquaporin-1 or Aquaporin1, Aqp1, of 258 aas and 6 TMSs. Three Aqp1 isoforms are differentially regluated by the function of the vasotocin
(AVTR) and isotocin (ITR) receptors (Martos-Sitcha et al. 2015). Aqp1aa, one of two isoforms in teleosts, may play a role in spermatogenesis in Cynoglossus semilaevis (Guo et al. 2017).

Aquaporin-3, Aqp-3 of 271 aas. Transports water, glycerol, hydrogen peroxide and urea (Geadkaew et al. 2015). AQP3 induces the production of
chemokines such as CCL24 and CCL22 through regulating the amount of cellular H2O2 in M2 polarized
alveolar macrophages, implying a role of AQP3 in asthma (Ikezoe et al. 2016).

Aquaporin x5 of 273 aas and 6 TMSs, Aqp-x5. The sequence reveals a mercurial-sensitive cysteine and a putative phosphorylation motif site for protein kinase A at Ser-257 (Kubota et al. 2006). A swelling assay using Xenopus oocytes revealed that AQP-x5 facilitated water permeability. Expression of AQP-x5 mRNA was restricted to the skin, brain, lungs and testes. Immunofluorescence and immunoelectron microscopical studies using an anti-peptide antibody (ST-156) against the C-terminal region of the AQP-x5 protein revealed the presence of immunopositive cells in the skin, with the label predominately localized in the apical plasma membrane of the secretory cells of the small granular glands. These glands are unique both in being close to the epidermal layer of the skin and in containing mitochondria-rich cells with vacuolar H+-ATPase dispersed among its secretory cells. Results from immunohistochemical experiments on the mucous or seromucous glands of several other anurans verified this result (Kubota et al. 2006).

Aquaporin 3. 95% identical to the human orthologue. Poorly permeable to water, but more permeable to glycerol and arsenic trioxide (Palmgren et al. 2017). It is expressed in the plasma membrane of basal epidermal cells in the skin; loss of function prevents skin tumorigenesis and epidermal cell proliferation (Hara-Chikuma and Verkman, 2008). The human orthologue also transports both water and glycerol and is the predominant AQP in skin (Jungersted et al. 2013). It's function is necessary for normal proliferation of colon cancer cells due to glycerol uptake (Li et al. 2016). Aqp3 is implicated in cancer progression to the metastatic state as its function promotes cell migration and cell shape plasticity. Its synthesis is regulated by the AhR (aryl hydrocarbon (pollutant) receptor or dioxin receptor), a transcription factor triggered by environmental pollutants (Bui et al. 2016). Trefoil factor (TFF) peptides increase cell water permeability and induce prodcution of Aqp3 (Marchbank and Playford 2018).

Major aquaglyceroporin, LmAQP1: transports water, glycerol, methylglyoxal, trivalent metalloids such as arsenite and antimonite, dihydroxyacetone and sugar alcohols. Also takes up the activated form or the drug, pentostam. It localizes to the flagellum of the Leishmania promastigotes and is used to regulate volume in response to hypoosmotic stress, functions in osmotaxis) (Figarella et al., 2005; Gourbal et al, 2004).

Glycerol/water/urea/arsenic trioxide-transporting channel protein, aqaporin 7 or Aqp7, but water is a poor substrate (Palmgren et al. 2017). Present in adipose tissue where it allows glycerol efflux. Defects result in increased accumulation of triglycerides, obesity and adult onset (type 2) diabetes (Lebeck 2014). It may be a drug target for anti-type 2 diabetes (Méndez-Giménez et al. 2018). AQP-7- and AQP-9-mediated glycerol transport in tanycyte cells may be under hormonal control to use glycerol as an energy source during the mouse estrus cycle (Yaba et al. 2017). It may also influence whole body energy metabolism (Iena and Lebeck 2018).

Aqp9 or Aqp-h9 of 294 aas. Takes up glycerol as well as water, and thereby contributes to freeze tolerance (Hirota et al. 2015). An almost identical orthologue, HC-9 in Dryophytes chrysoscelis (gray treefrog), similarly facilitates glycerol permeability. Both the transcriptional and translational levels of HC-9 change in response to thermal challenges, with a unique increase in liver during freezing and thawing (Stogsdill et al. 2017).

Aqp1 of 304 aas and 6 TMSs; the most abundant transmembrane protein in the tegument of Schistosoma mansoni.
This protein is expressed in all developmental stages and seems to be essential in parasite survival
since it plays a crucial role in osmoregulation, nutrient transport and drug uptake (Figueiredo et al. 2014).

Endoplasmic reticulum Small and Basic Intrinsic Protein; (SIP1;1) water channel (present in all plant tissues except seeds) (Ishikawa et al., 2005) May play a role in gas and water exchange between the plant and its environment via stromata (turgor-driven epidermal valves) and the hydathode pore (Pillitteri et al., 2008).

The Aquaporin-8 (Aqp8) transporter is permeable to water, NH3, formamide and H2O2, and it is present in the inner membrane of mitochondria and the plasma membrane (Bienert et al., 2007; Saparov et al., 2007; Soria et al., 2010). Cholesterol, via sterol regulatory element-binding protein (SREBP) transcription factors, activates or represses genes involved in its hepatic biosynthetic pathway, and also modulates the expression of hepatocyte mitochondrial aquaporin-8 (mtAQP8), a channel that can function as peroxiporin by facilitating the transmembrane diffusion of H2O2. The peroxiporin, mtAQP8, plays a role in the SREBP-controlled hepatocyte cholesterogenesis (Danielli et al. 2019).

Aqp8a.1 of 260 aas and 6 TMSs. The spaciotemporal pattern of induction of three aquaporins during embyonic development in Zebrafish has been determined, and all three, Aqp8a.1, Aqp8a.2 and Aqp8b, show distictive patterns (Koun et al. 2016).

Plasma membrane intrinsic protein 2a (forms active heterotetramers with PIP1;1 (TC# 1.A.8.11.3); down regulated under drought stress (Najafabadi et al., 2008). Transports H2O2 (Dynowski et al., 2008). The Mesembryanthemum crystallinum PIP2;1 orthologue is an aquaporin impermeable to urea and glycerol. It is positively regulated by PKA- and PKC- mediated phosphorylation (Amezcua-Romero et al., 2010). PIP1;1 and PIP2;2 (Q9ATM8) co-expression modulates the membrane water permeability in the halophyte Beta vulgaris storage root through a pH regulatory response, enhancing membrane versatility to adjust its water transfer capacity (Bellati et al., 2010). The wheat orthologue has been described (Ayadi et al., 2011). Inter-TMS interactions occurring both within and between
monomers play crucial roles in tetramer formation, and assembly of tetramers is critical for their trafficking from the ER to the plasma membrane as well as
water permeability (Yoo et al. 2016). This protein as well as 1.A.8.11.6 is possibly orthologous to spinach
PIP1;2 for which the crystal structure is available (PDP# 4JC6) (Berny et al. 2016). Plays a role in drought and salt tolerance (Wang et al. 2015). PIP-type aqauporins may also transport CO2, boric acid, glycerol, arsenic and Na+ (Byrt et al. 2017).

Aquaporin PIP2;5 (PIP2-5) of 285 aas. Transports water and hydrogen peroxide (H2O2) (Bienert et al. 2014). PIP1;2 doesn't transport H2O2. TMS3 contains an LxxA motif that targets the protein to the plasma membrane from the ER. While PIP2s are in the plasma mebrane, PIP1s are retained in the ER; this motif only partly explains the difference (Chevalier and Chaumont 2015). PIP1;2 AND PIP2;5 form homo- and heterotetramers (Berny et al. 2016).

Aqp2 of 297 aas and 6 TMSs. Induced by both NH3 and CO2, and transports both gases. Aqp2 is found in the plasma membrane and may be involved in photoprotection. It may
facilitate the efflux of NH3, preventing the uncoupling effect of high
intracellular ammonia concentrations (Matsui et al. 2018).

The root-expressed MIP transporter of lactic acid, NIP2;1 (Nod26-like MIP-4; NLM4) (induced by water logging and anoxic stress; shows minimal water and glycerol transport). It may play a role in adaptation to lactic fermentaion under anaerobic stress (Choi and Roberts, 2007). Lactic acid transport is induced by anoxic stress (Choi and Roberts, 2007).

Hg2+-inhibitable aquaporin, AqpM (transports both water and glycerol as well as CO2) (Kozono et al., 2003; Araya-Secchi et al., 2011). Its 3-d structure has been determined to 1.7 Å. In AqpM, isoleucine replaces a key histidine residue found in the lumen of water channels, which becomes a glycine residue in aquaglyceroporins. As a result of this and other side-chain substituents in the walls of the channel, the channel is intermediate in size and exhibits differentially tuned electrostatics when compared with the other subfamilies (Lee et al. 2005).